Objective: Melanoma is among the top six cancers as a cause of death and morbidity. Unfortunately there has been little progress in the medical treatment of metastatic melanoma, because of its resistance to current chemotherapeutic agents. In view of this, there is much interest in the identification of new agents for the treatment of melanoma. Rose Bengal (RB) has been used as a systemic diagnostic of hepatic function, ophthalmic diagnostic and photosensitiser in photodynamic treatment. In the present study, effects of RB, not as a photosensitiser, was tested in melanoma cells in the absence of light.Materials and Methods: Human melanoma cell lines, Me4405, Me1007, IgR3, Mel-FH, Mel-RM, Mel-CV, MM200, Sk-Mel-28 and fibroblast cells were cultured in DMEM medium. Cell death was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak).Results: The result showed RB could induce pronounced cell death in different melanoma cell lines but not in fibroblast cells. This toxicity was predominantly induced by non-apoptotic cell death but in some cell lines, RB could also induce apoptotic cell death.Conclusion: RB may be considered as a promising chemotherapeutic agent for the treatment of melanoma in the future.